INS and obesity due to melanocortin 4 receptor deficiency: CerS2ΔBKO and control mice were phenotyped in three different paradigms of β-cell stress: normal diet feeding (ND, low insulin demand), obesogenic high-fat-diet feeding (HFD, intermediate insulin demand), and when backcrossed onto a leptin-deficient (ob/ob) background (extreme insulin demand due to massive obesity) (Fig. 2a–s and Supplementary Fig. 1t,u).